Focused ultrasound-induced stimulation of microbubbles augments site-targeted engraftment of mesenchymal stem cells after acute myocardial infarction.

作者: Alexander Ghanem , Caroline Steingen , Florian Brenig , Fabienne Funcke , Zhi-Yong Bai

DOI: 10.1016/J.YJMCC.2009.06.008

关键词: EndotheliumBasement membraneTransplantationPathologyIn vivoImmunologyMyocardial infarctionMesenchymal stem cellCell therapyMedicineMicrobubbles

摘要: article i nfo Intravascular transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is a promising therapeutic approach after acute myocardial infarction. Efficacy and targeting cell engraftment are crucial variables determining the value MSC transplantation. Highly focused ultrasound- mediated stimulation microbubbles (hf-UMS) allows locoregional pre-treatment target tissue. In "proof concept" study, we investigated augmentation site-targeted with hf-UMS. We further evaluated ability transplanted MSCs to transmigrate across endothelial barrier into non- ischemic post-ischemic myocardium in vivo. After ischemia reperfusion, rats received hf-UMS on anterior left-ventricular wall followed by intravascular MSCs. Global regional was quantified means confocal laser- scanning microscopy; adhesion, transendothelial migration invasion basement membrane were distinguished. Targeted exhibited higher amount vs. non-targeted The rate lowest non-ischemic (41.2±2%) compared post- (53±5.7%, pb0.01). Hf-UMS significantly increased transmigration 50± 6.1% (pb0.05) 64±8.9% (pb0.05), respectively. Additionally, segments exposed revealed an onset protease activity. Signs undesired biological effects, such as induction apoptosis and/or necrosis not observed. This study provides first evidence endothelium only improves but also myocardium.

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